Molecular proof for Lophomonas infection in a patient with history of breast cancer

Abstract We report a 52‐year‐old patient with a history of breast cancer (BC) referred to the clinic of Afzalipour Hospital, in Kerman, eastern Iran, with a 1‐week complaint of restless dyspnea. A chest computed tomography scan revealed consolidations in the upper lobes of both lungs. The patient had no history of smoking or underlying diseases that would predispose her to consolidation, including pneumonia. Then, bronchoscopy was performed for the patient, and bronchoalveolar lavage fluid was sent to the Iranian National Registry Center, where the Lophomonas parasite was detected in the sample and confirmed using a polymerase chain reaction test. Finally, her symptoms improved by receiving oral metronidazole three times a day for 3 weeks.


INTRODUCTION
Breast cancer (BC) is the second leading cause of cancer death in women in the United States, accounting for nearly 40,000 deaths each year, and is the most commonly diagnosed cancer in females globally. 1 The immune system is suppressed in the early stages of this cancer, both during the disease by alterations in T-cells and as a result of chemotherapy drugs, such as docetaxel and trastuzumab. [2][3][4] Febrile neutropenia and many opportunistic infections can develop during this immunosuppression, including candidiasis and parasitic infections such as Toxoplasma gondi. [4][5][6] Lophomonas blattarum (L. blattarum) is an anaerobic protozoan cell which inhabits cockroaches' guts. Its cysts can be found in the faeces of these insects, and humans are usually infected through inhalation of cyst-containing aerosols. L. blattarum is the main cause of lophomoniasis, a parasitic chronic respiratory infection which results in fever, pneumonia and chronic expectorating coughs. 7,8 This parasite has been observed to infect those with a suppressed immune system 9 and to cause lung cavities. 10 Considering its effects on the respiratory system, particularly in immunocompromised patients, and the fact that it can simply be treated with metronidazole, it is essential to be aware of this protozoa and treat it effectively. Herein, we report a case of Lophomonas infection in a BC patient.

CASE REPORT
On 2021, a 52-year-old housewife with underlying BC was referred to the Afzalipour Hospital, Kerman, Kerman province, eastern Iran, with a 1-week complaint of dyspnea at rest. She had not yet taken any medications. She had no history of asthma or cardiovascular disease such as myocardial infarction, did not smoke or abuse drugs, and had no history of asbestos exposure, trauma, weight loss, or night sweats. She was conscious and oriented. Vital signs included (BP: 130/90 mmHg, HR: 98 beats/min, RR: 20, T: 38.8 C, SpO 2 : 94%). She had crackles in both lungs during the physical examination, while other organ examinations were unremarkable.
The patient's primary laboratory tests, which included CBC, fasting blood sugar, Na, K, Cr, TSH, LFT, ECG and other laboratory tests, were normal except a slight increase in levels of ESR, CRP and a mild decrease in haemoglobin (Table 1). A COVID-19 real time polymerase chain reaction (RT-PCR) test was requested, but the results were negative. Blood and sputum cultures were negative. When a chest radiograph revealed suspicious consolidations, a chest computed tomography (CT) scan was ordered, which revealed consolidations in the upper lobes of both lungs. For further evaluation, we requested a pulmonologist consultation. The pulmonologist advised performing a bronchoscopy because of the underlying BC.
A bronchoscopy was performed on the patient, and bronchoalveolar lavage fluid (BALF) samples were collected. One sample was sent to the microbiology laboratory to check for bacterial infection, and another sample was sent to Iranian National Registry Center for Lophomoniasis (INRCL) to examine for Lophomonas parasite. A wet smear prepared from BALF sediment revealed the presence of a few Lophomonas live and motile flagellated parasites ( Figure 1). In the meantime, a conventional PCR test 8 was performed on the sample, which confirmed the microscopic results. This patient received oral metronidazole 500 mg every 8 h for 3 weeks, which improved the patient's symptoms. On a 3-month follow-up, the patient had no respiratory complaints and her physical examination and laboratory tests were normal.

DISCUSSION
Consolidations in the lungs are caused by different diseases, such as infections, infarction and contusion, malignancies such as lymphomas, haemorrhages, and rheumatologic and immunologic disorders. [11][12][13] Most commonly, infectious diseases, such as pneumonia are the source, and among them, bacteria, fungi and protozoa, are the most common pathogens. 14,15 This patient had risk factors for Lophomonas infection, including immunosuppressed status and contact with cockroaches in her house. 8,16 Our report is consistent with other reports which suggest that Lophomonas is more common in immunosuppressed patients. A study by He et al. 17 reported two cases of lophomoniasis in transplant recipients. Also, Woerden et al. 18 found that flagellated protozoa in sputum are more prevalent in asthmatic patients who received corticosteroids compared to the control group. Wahid et al. 19 presented Lophomonas in a 29-year-old female with systemic lupus erythromatosus. Although many studies have reported eosinophilia as the main result in CBC, but it was not seen in our patient which could be due to her immunocompromised state, 16,20 which is consistent with Wahid et al. report. 19 Lophomonas can be diagnosed under light microscopy, but it is hard for an unskilled parasitologist to differentiate between Lophomonas and normal bronchial epithelium due to their analogy. 8,16,21 But our colleagues have demonstrated a molecular PCR based diagnosis with more sensitivity and more specificity. 8,22 Our patient's symptoms improved with metronidazole administration. This drug is also effective in treating anaerobic respiratory infections and those infections could have been a probable cause, but her laboratory tests and cultures for bacterial infections, both aerobic and anaerobic, were negative.
This case presentation strongly persuade us to pay additional deliberation to this newly emerging pulmonary pathogen. As a conclusion, lophomoniasis should be considered in the differential diagnosis of each patient with lung consolidations, especially in immunocompromised conditions such as malignancies. Therefore, extra attention should be focused on pulmonary consolidations in patients with BC.

AUTHOR CONTRIBUTION
Mahdi Fakhar and Ahmad Shafahi involved in interpretation and collecting of data. Ali Sharifpour, Amirmasoud Taheri and Erfan Ghadirzadeh were writing and editing of the manuscript. Mahdi Fakhar and Mostafa Soleymani involved in editing and preparing the final version of manuscript. All authors reviewed the paper and approved the final version of the manuscript.

CONFLICT OF INTEREST
None declared.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author.

ETHICS STATEMENT
The authors declare that appropriate written informed consent was obtained for the publication of this manuscript and accompanying images.